Heart failure is a clinical problem of great magnitude in which the complex mechanisms, natural history and therapeutic options remain largely unexplored. It is now apparent that the syndrome represents an interaction of disturbed myocardial function with altered peripheral vascular function. The relative role of the heart and the periphery in influencing the progressive course of this disease process is still unclear. This Program Project is aimed at exploring potentially important myocardial factors and neurohumoral influences on the peripheral vasculature that may play a critical role in the progression of heart failure in experimental models and in man. Myocardial factors to be studied include: (1) genetic disease of the myocardium in the turkey; (2) myocardial necrosis in the dog; (3) myocardial toxins in the turkey; (4) myocardial ischemia in the dog; (5) myocardial infarcts in the rat; (6) pressure overload in the rat; and (7) ischemic and non-ischemic myocardial dysfunction in man. Neurohumoral and peripheral vascular studies will include: (1) pre-synaptic and post-synaptic Alpha-adrenoreceptor function; (2) beta-adrenoreceptor function and down-regulation; (3) renin-angiotensin stimulation and blockade; (4) vasopressin-induced vasoconstruction; (5) vascular impedance measurements; (6) regional blood flow measurements; (7) atrial natriuretic peptide measurements; and (8) measurement of sympathetic nerve traffic. The seven projects and four cores that constitute the Program are heavily dependent on certain methodology including nuclear magnetic resonance spectroscopy, measurement of plasma and tissue catecholamines, assessment of adrenoreceptor sensitivity and density, microsphere measurement of blood flow distribution and exercise as a stress to the myocardium and peripheral vasculature. The strength to be gained from the Program Project concept is the sharing of ideas, experimental methods, blood samples and tissue, and biometric and administrative support that a joint effort will facilitate.